Various technologies exist in which parts of an animal or human body may be imaged so as to aid in diagnosis and therapy. Some of these existing techniques are described in this section.
One of the most well known imaging techniques involves the use of X-rays to visualize skeletal and other internal structures within animals and humans. There are, however, a number of problems associates with the use of X-rays. First, some areas of the body may not be X-rayed safely. In addition, X-rays are dangerous if the amount of exposure is excessive; further, all X-ray radiation absorbed over a lifetime is cumulative. Finally, while X-rays may produce images of the skeletal and other internal structures, X-rays have proved to be relatively unsatisfactory for detailed viewing of certain organ systems and blood vessels.
Another widely used technique is angiography, whereby a radio-opaque dye is injected into an artery. Because the dye highlights the arteries through which it flows, an X-ray may be used to obtain an image of major, large arteries and their significant branches. However, angiography does not permit visualization of under-perfused, ischemic areas of tissue or heart muscle, or the microcirculation. In addition, certain angiographic observations are based upon measurements which may vary depending upon the appparatus used, the placement and angle of lenses, operator skill and similar factors. Moreover, angiography is invasive in that it requires the placement of a catheter into arteries as opposed to veins. Besides requiring hospitalization, angiography may be dangerous.
Another technique, often referred to as radio-nuclide imaging, involves the injection of radioactive substances, such as thallium, into the bloodstream. This technique does not require invasion of the arteries as does angiography, but it does require the use of very expensive and sophisticated machinery. Further, radionuclide imaging produces images of only a limited number of view of the heart, and those images may not be of exceptional clarity. Finally, this type of radiation is cumulative over a lifetime and may be dangerous.
Recently, there have been advances in techniques for ultrasonically imaging various parts of the body; these techniques when applied to the heart in particular are known as "echocardiorgraphy". An ultrasonic scanner is used to generate and receive sound waves. The ultrasonic scanner is placed on the body surface overlying the area to be imaged. The sound waves generated by the scanner are directed toward the area to be imaged. The scanner then detects sound waves reflected from the underlying area and translates that data into images.
While such ultrasonic scanners are known in the art, a brief review will be set forth in order to more fully explain the present invention. When ultrasonic energy is transmitted through a substance, the acoustic properties of the substance will depend upon the velocity of the tranmission and the density of the substance. Changes in the substance's acoustic properties (or acoustic impedance) will be most prominent at the interface of different substances (i.e., solids, liquids and gases). As a consequence, then ultrasonic energy is directed through various media, the changes in acoustic properties will change the reflection characteristics, resulting in a more intense sound reflection signal received by the ultrasonic scanner.
Early ultrasonic imaging techniques such as echocardiograms suffered from a lack of clarity. As a result, extensive efforts were undertaken to improve the ultrasonic scanners and related equipment. In addition, beginning in 1968, "contrast" agents were injected into the bloodstream in an effort to obtain clearer or "enhanced" ultrasonic images. The prior art contrast agents were liquids containing microbubbles of gas, which sometimes were claimed to be encapsulated with gelatin (see U.S. Pat. No. 4,276,885) or saccharin and sometimes were produced by mechanically agitating, i.e., handshaking, mixtures of various liquids. Other prior art contrast agents are disclosed in an article by J. Ophir, et al. entitled "Ultrasonic Backscatter from Contrast Produced by Collagen Microspheres" in Ultrasonic Imaging 2 (1980), pp. 67-77.
The contrast agents themselves are intense sound wave reflectors because of the acoustic differences between the liquid and the gas microbubbles dissolved therein; thus, when the contrast agents are injected into and perfuse the microvasculature of tissue, clearer images of such tissue may be produced. However, notwithstanding the use of such contrast agents, the image produced, for example, of the myocardial tissue, is of relatively poor quality, is highly variable and is not quantifiable due to the variable size and persistance associated with prior art microbubbles. Further, the problems of air embolism toxicity have not yet been investigated.